The range of aging rates among animals is enormous. Both exceptionally slow and fast aging rates have evolved repeatedly. Within mammals, for instance, a comparatively species-poor group, there have been a m/n/mum of 9 instances of the independent evolution of exceptionally slow-aging. Are the cellular and molecular mechanisms underlying these separate evolutionary extensions of life similar, or are there many ways for nature to produce exceptionally slow aging? To what extent does cellular stress-resistance, commonly found associated with extended longevity in model organisms, comprise a general mechanism of aging? Are there gene expression "signatures" that distinguish long- vs short-lived organisms, and could such signatures help identify fundamental aging processes? Are genetic alterations that lengthen life in the small array of"model organisms," such as worms and flies more broadly relevant across mammals, particularly with respect to long-lived species? Until recently, such questions were impossible to address in a comparative context. However advances in gene sequencing capability, phylogenetic information, and the implementation of high-throughput gene expression profiling techniques have now made these questions tractable. The proposed study will employ nine mammal species, carefully selected for their phylogenetic position and relative aging rates, to: (1) assess the extent to which cellular stress-resistance correlates with aging rate among mammals, and determine the utility of using cellular response to stress as a model and perhaps mechanism for modulation of senescence; (2) broadly compare induced gene expression differences associated with differing levels of cellular stress resistance across our spectrum of long- and short-lived species. A key feature of this specific aim is the development of a "universal mammalian microarray," specially designed for comparative mammalian aging studies; (3) broadly investigate the details of mitochondrial function across our range of long- and short-lived species to address the extent to which some common mitochondrial phenotype (e.g. low ROS production per level of electron flux) might generally affect aging rate.